The invention is a solid transdermal therapeutic system with UV absorber. The UV-stable transdermal therapeutic system (TTS) is particularly designed for photosensitive active pharmaceutical ingredients. It comprises a backing layer 1, of at least one active ingredient-containing matrix 2, and of a detachable protective film 3. However an adhesive layer 4 and a separating layer 5 can optionally be introduced between the backing layer 1 and the active ingredient-containing matrix 2. At least one hydroxyphenyltriazine acting as UV absorber can be embedded in the backing layer 1, in the active ingredient-containing matrix 2, or in the adhesive layer 4.
Transdermal therapeutic systems, which contain a gestagen and/or an estrogen, are suitable for controlling fertility.
Attempts to employ photosensitive active ingredients, which absorb UV-A and UV-B rays, customarily used in sun creams, are known, as described by Briscart & Plaizier-Vercammen (Proc. 2nd World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, APGI/APV, 1998, 1231-1232).
The patent literature further discloses the protection of transdermal therapeutic systems (TTS) provided with photosensitive active ingredients by visually conspicuous aluminized or lacquered covering films as backing layers of the TTS.
WO-A1-00/56289 describes a method for protecting therapeutic preparations, systems or their constituents, the intention being to achieve in each case specific protection from degradation by harmful factors, such as atmospheric oxygen, water, and/or light. Photo-protective substances, which absorb or reflect electromagnetic waves, are used, employing respectively absorbents or reflectants whose absorption or reflection spectrum covers the wave-length range responsible for the instability of the photosensitive substance or its constituents. Colored plastic films are used, inter alia, in this case as covering film, indicated by example of the 1,4-dihydopyridine derivative lacidipine.
The coloring of highly flexible plastic films proves to be difficult and does not provide reliable photo-protection owing to the frequently occurring fissures in the colored layer of the plastic film.
WO-A2-02/34200 further discloses transdermal therapeutic systems (TTS), which consist of an active ingredient-containing polymer matrix and of a backing layer. The polymer matrix and the backing layer are firmly connected or form a laminate. Both the polymer matrix and the backing layer comprise a colorless system, which absorbs in the UV range but has no intrinsic pharmacological effect. EP-A1-1452173 describes transdermal therapeutic systems, which consist of a backing layer, of at least one active ingredient-containing matrix and optionally of a detachable film and comprises a UV absorber. At least one UV absorber-containing adhesive layer is provided between the backing layer and the active ingredient-containing matrix furthest away from the surface of the skin. In addition, at least one separating layer, which is impermeable to active ingredient and impermeable to the UV absorber, is present between the adhesive layer containing the UV absorber and the active ingredient-containing matrix, which is furthest away from the surface of the skin. The UV absorber can be p-aminobenzoic acid, an aminobenzoic acid derivative, preferably 2-ethylhexyl 4-dimethyl-amino-benzoate and/or polyethoxyethyl 4-bis-(polyethoxyl)amino-benzoate, cinnamic acid, a cinnamic acid derivative, preferably isoamyl 4-methoxycinnamate or 2-ethylhexyl 4-methoxycinnamate, 3-benzylidenebornan-2-one, a benzylidene bornan-2-one derivative, preferably 3-(4′)-methylbenzylindenebornan-2-one, 3-(4-sulphone)-benzylidenebornan-2-one, or 3-(4′-trimethylammonium)-benzylidenebornan-2-one methylsulphate, salicylic acid derivative, preferably 4-isopropylbenzyl salicylate, 2-ethylhexyl salicylate, or 3,3,5-trimethylcyclohexyl salicylate, a benzotriazole, preferably 2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1-dimethylethyl)-4-methyl-phenol, 2,4,6′-trianiline-p-(carbo-2′-ethylhexyl-1′-oxy)-1,3,5-triazine, 3-imidazol-4-yl-acrylic acid, 3-imidazol-4-yl-3-imidazol-4-yl-acrylic ester, 2-phenylene benzimidazole-5-sulphonic acid, or its K, Na and triethanolamine (=TEA) salt, 2-cyano-3, 3-diphenylacrylic acid, terephthaloylidene-dicamphorsulphonic acid, butylmethoxy-dibenzoylmethane, benzophenone, or a benzophenone derivative, preferably benzophenone-3 or benzophenone4.
The known solutions have the disadvantage                that the protective effect produced by the added UV absorber for the active ingredient is incomplete,        that owing to the incomplete protective effect in some cases higher concentrations of UV absorbers must be employed, which may have adverse effects on the compatibility of the TTS with skin.        